[unreadable] Project Summary. Dr. Ryan is currently a post-doctoral fellow in the Division of Endocrinology, Emory University School of Medicine. Dr. Ryan has already published 3 first author papers in the field of immunology, and her first, first author paper in the field of osteoimmunology has recently been accepted to the Proceedings of the National Academy of Sciences. The goal of this application is to give Dr. Ryan the necessary skills and experience to become an independently funded primary investigator in the field of osteoimmunology. Upon successful award of this application, Dr. Ryan will be promoted to Instructor of Medicine. Her career development plan includes a cross-discipline research experience, development of skills and experience in the analysis and implementation of techniques related to the field of bone biology, attendance at national meetings, and development of excellent oral and written communication skills. During the time period of support, Dr. Ryan will complete the research plan as outlined below and become increasingly independent, as well as spend a portion of the final year of support to developing new ideas and submitting applications for independent funding. The Division of Endocrinology, Metabolism and Lipids is an excellent environment for Dr. Ryan's career development, as it is staffed by over 25 full-time clinician- teachers, physicians-investigators, M.D. and Ph.D. scientists involved in research ranging from diabetes, osteoporosis and bone biology, nutrition and obesity. This environment will give Dr. Ryan a soild foundation in research in the field of bone biology. The goal of the research in this application is geared towards proving the hypothesis that the estrogen deficiency driven increase in the peripheral T cell pool is due to increased thymic output, and activation of antigen presentation leading to enhanced CD4 to CD8 crosstalk that is essential for the activation and recruitment of T cells to the resorption surface of bone. To accomplish this, Dr. Ryan will show that estrogen deficiency induces cross talk between CD4 and CD8 T cells, she will identify the anatomical sites of T cell activation, and she will quantitate the contribution of thymic output to the mechanisms of estrogen deficiency induced bone loss in aged mice. Relevance: Understanding the nature and distribution of the activated T cells involved in ovx induced bone loss may ultimately lead to novel therapeutic approaches to preventing or ameliorating postmenopausal osteoporosis. [unreadable] [unreadable]